Influences on older people’s decision making regarding choice of topical or oral NSAIDs for knee pain: qualitative study

Objective To explore the factors that influence older people’s decision making regarding use of topical or oral ibuprofen for their knee pain.Design Qualitative interview study nested within a randomised controlled trial and a patient preference study that compared advice to use oral or topical non-steroidal anti-inflammatory drugs (NSAIDs) for knee pain in older people.Setting 11 general practices.Participants 30 people aged ≥50 with knee pain. Results Participants’ decision making was influenced by their perceptions of the associated risk of adverse effects, presence of other illness, nature of their pain, advice received, and practicality. Although participants’ understanding of how the medications worked was sometimes poor their decision making about the use of NSAIDs seemed logical and appropriate. Participants’ model for treatment was to use topical NSAIDs for mild, local, and transient pain and oral NSAIDs for moderate to severe, generalised, and constant pain (in the absence of other more serious illness or risk of adverse effects). Participants showed marked tolerance and normalisation of adverse effects.Conclusion Participants had clear ideas about the appropriate use of oral and topical NSAIDs. Taking such views into account when prescribing may improve adherence, judgment of efficacy, and the doctor-patient relationship. Tolerance and normalisation of adverse effects in these patients indicate that closer monitoring of older people who use NSAIDs might be needed.     

Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials

Objective To assess the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis.Data sources Medline, Embase, Scientific Citation Index, CINAHL, Cochrane Library, and abstracts from conferences.Review methods Inclusion criterion was randomised controlled trials comparing topical NSAIDs with placebo or oral NSAIDs in osteoarthritis. Effect size was calculated for pain, function, and stiffness. Rate ratio was calculated for dichotomous data such as clinical response rate and adverse event rate. Number needed to treat to obtain the clinical response was estimated. Quality of trial was assessed, and sensitivity analyses were undertaken.Results Topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis only in the first two weeks of treatment. Effect sizes for weeks 1 and 2 were 0.41 (95% confidence interval, 0.16 to 0.66) and 0.40 (0.15 to 0.65), respectively. No benefit was observed over placebo in weeks 3 and 4. A similar pattern was observed for function, stiffness, and clinical response rate ratio and number needed to treat. Topical NSAIDs were inferior to oral NSAIDs in the first week of treatment and associated with more local side effects such as rash, itch, or burning (rate ratio 5.29, 1.14 to 24.51).Conclusion Randomised controlled trials of short duration only (less than four weeks) have assessed the efficacy of topical NSAIDs in osteoarthritis. After two weeks there was no evidence of efficacy superior to placebo. No trial data support the long term use of topical NSAIDs in osteoarthritis.     

Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial

Background

Treatment of osteoarthritis with oral NSAID therapy provides pain relief but carries a substantial risk of adverse effects. Topical NSAID therapy offers an alternative to oral treatment, with the potential for a reduced risk of side effects. The objective of this trial was to assess the safety and efficacy of a topical diclofenac solution in relieving the symptoms of primary osteoarthritis of the knee.

Methods

We identified 248 men and women from southern Ontario with primary osteoarthritis of the knee and at least moderate pain. The patients were randomly assigned to apply 1 of 3 solutions to their painful knee for 4 weeks: a topical diclofenac solution (1.5% wt/wt diclofenac sodium in a carrier containing dimethyl sulfoxide [DMSO]); a vehicle-control solution (the carrier containing DMSO but no diclofenac); and a placebo solution (a modified carrier with a token amount of DMSO for blinding purposes but no diclofenac). The primary efficacy end point was pain relief, measured by the Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis Index pain subscale. Secondary end points were improved physical function and reduced stiffness (measured by the WOMAC subscales), reduced pain on walking and patient global assessment (PGA). Safety was evaluated with clinical and laboratory assessments.

Results

In the intent-to-treat group the mean change (and 95% confidence interval [CI]) in pain score from baseline to final assessment was significantly greater for the patients who applied the topical diclofenac solution (–3.9 [– 4.8 to –2.9]) than for those who applied the vehicle-control solution (–2.5 [– 3.3 to –1.7]; p = 0.023) or the placebo solution (–2.5 [–3.3 to –1.7]; p = 0.016). For the secondary variables the topical diclofenac solution also revealed superiority to the vehicle-control and placebo solutions, leading to mean changes (and 95% CIs) of –11.6 (–14.7 to –8.4; p = 0.002 and 0.014, respectively) in physical function, –1.5 (–1.9 to –1.1; p = 0.015 and 0.002, respectively) in stiffness and –0.8 (–1.1 to –0.6; p = 0.003 and 0.015, respectively) in pain on walking. The PGA scores were significantly better for the patients who applied the topical diclofenac solution than for those who applied the other 2 solutions (p = 0.039 and 0.025, respectively). The topical diclofenac solution caused some skin irritation, mostly minor local skin dryness, in 30 (36%) of the 84 patients, but this led to discontinuation of treatment in only 5 (6%) of the cases. The incidence of gastrointestinal events did not differ between the treatment groups. No serious gastrointestinal or renal adverse events were reported or detected by means of laboratory testing.

Interpretation

This topical diclofenac solution can provide safe, site-specific treatment for osteoarthritic pain, with only minor local skin irritation and minimal systemic side effects.Osteoarthritis is a degenerative joint disease affecting articular cartilage and underlying bone, commonly of the knee.¹ Current treatment includes the oral use of NSAIDs, either nonselective or cyclooxygenase-2 (COX-2)-selective. These agents carry a substantial risk of clinically significant adverse effects, particularly on the gastrointestinal^2,3 and renal systems.⁴ Although the incidence of gastrointestinal complications has been reported to be lower with COX-2-selective NSAIDs than with nonselective NSAIDs,^5,6,7 the former have been linked to adverse renal effects⁸ and an increased risk of cardiovascular complications.⁹The need for safer treatment of osteoarthritis has led to research into the topical use of NSAIDs.^10,11,12 Recent reviews of the few published placebo-controlled studies suggest that topical NSAID therapy can relieve pain^13,14,15 with few gastrointestinal side effects.¹⁶ Current practice guidelines advocate the use of topical therapy, including NSAIDs, in the management of osteoarthritis.^17,18,19 A diclofenac solution containing the absorption enhancer dimethyl sulfoxide (DMSO) was developed for site-specific topical application. The objective of this study was to demonstrate that applying this solution to a painful knee with primary osteoarthritis could provide symptom relief with minimal systemic side effects.     

The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis

Objective: To assess the efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis (OA).Methods: The databases such as Pubmed and Cochrane Library were searched to collect the article about Curcuma longa extract and curcumin in the treatment of OA. Then, randomized controlled trials (RCTs) were selected and their data were extracted. Finally, the RevMan5.3 was utilized for risk of bias assessment and meta-analysis, the STATA15.0 were utilized for publication bias assessment, and GRADE tool were used for the evidence quality assessment of primary outcomes.Results: A total of 15 RCTs involving 1621 participants were included. (1) Compared with placebo, Curcuma longa extract and curcumin (C.) can decrease the visual analog scale (VAS) and The Western Ontario and McMaster Universities (WOMAC) score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, Curcuma longa extract and curcumin are comparable with those of placebo. (2) Compared with non-steroidal anti-inflammatory drugs (NSAIDs), Curcuma longa extract and curcumin have similar effects on joint pain, function and stiffness. The incidence of adverse events in Curcuma longa extract and curcumin was lower. (3) Compared with the NSAIDs group, C.+NSAIDs can also decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, the addition of Curcuma longa extract and curcumin to NSAIDs did not increase adverse events.Conclusion: Curcuma longa extract and curcumin may be a safer and effective supplement for OA patients. It is recommended to use Curcuma longa extract and curcumin supplement for OA patients for more than 12 weeks.     

Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center,randomized, open-label,non-inferiority trial

Introduction

While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA.

Methods

This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%.

Results

The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P = 0.026 and 0.004, respectively).

Conclusions

The early efficacy of IA-HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA-HA is superior to that of NSAIDs for patients with knee OA.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR), UMIN000001026.     

Behavioural activation to prevent depression and loneliness among socially isolated older people with long-term conditions: The BASIL COVID-19 pilot randomised controlled trial

BackgroundOlder adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to “shield” to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed.Methods and findingsWe undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of −0.50 PHQ-9 points (95% CI −2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI −1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI −0.51 to 1.06) and at 3 months −0.87 (95% CI −1.56 to −0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (−1.33, 1.73) and at 3 months 0.31 (−1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (−4.17, 4.85) and at 3 months 0.11 (−4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (−2.64, 5.15) and at 3 months 1.26 (−2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness.ConclusionsIn this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT).Trial registrationISRCTN94091479.

In a pilot randomised controlled trial, Simon Gilbody and colleagues present preliminary findings from a telephone delivered intervention (behavioural activation) designed to prevent depression and loneliness among socially isolated older people with long term conditions.     

Managing postoperative pain in adult outpatients: a systematic review and meta-analysis comparing codeine with NSAIDs

BACKGROUND:Analgesics that contain codeine are commonly prescribed for postoperative pain, but it is unclear how they compare with nonopioid alternatives. We sought to compare the effectiveness of codeine and nonsteroidal anti-inflammatory drugs (NSAIDs) for adults who underwent outpatient surgery.METHODS:We conducted a systematic review and meta-analysis of randomized controlled trials comparing codeine and NSAIDs for postoperative pain in outpatient surgery. We searched MEDLINE and Embase from inception to October 2019 for eligible studies. Our primary outcome was the patient pain score, converted to a standard 10-point intensity scale. Our secondary outcomes were patient-reported global assessments and adverse effects. We used random-effects models and grading of recommendations assessment, development and evaluation (GRADE) to assess the quality of evidence.RESULTS:Forty studies, including 102 trial arms and 5116 patients, met inclusion criteria. The studies had low risk of bias and low-to-moderate heterogeneity. Compared with codeine, NSAIDs were associated with better pain scores at 6 hours (weighted mean difference [WMD] 0.93 points, 95% confidence interval [CI] 0.71 to 1.15) and at 12 hours (WMD 0.79, 95% CI 0.38 to 1.19). Stronger NSAID superiority at 6 hours was observed among trials where acetaminophen was coadministered at equivalent doses between groups (WMD 1.18, 95% CI 0.87 to 1.48). NSAIDs were associated with better global assessments at 6 hours (WMD −0.88, 95% CI −1.04 to −0.72) and at 24 hours (WMD −0.67, 95% CI −0.95 to −0.40), and were associated with fewer adverse effects, including bleeding events.INTERPRETATION:We found that adult outpatients report better pain scores, better global assessments and fewer adverse effects when their postoperative pain is treated with NSAIDs than with codeine. Clinicians across all specialties can use this information to improve both pain management and opioid stewardship.

Outpatient surgical procedures are now more common than inpatient procedures, given the development of less invasive techniques, the drive for health care efficiency, and improvements in anesthesia and pain management. ^1–4 Postoperative pain management after outpatient procedures often includes low-potency or low-dose opioids.⁵ Codeine use is widespread in this setting and codeine remains the most commonly prescribed opioid in many countries, including Canada.^6–9 However, its efficacy is variable, its potency is low and its use is associated with risks of severe adverse effects and misuse.¹⁰ Amid the ongoing opioid crisis, management of pain and potential opioid misuse is important across all medical and dental specialties.¹¹Nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to low-potency opioids. The potency, effects and toxicity of NSAIDs depend on the degree to which they inhibit cyclooxygenase 1 and 2 activity. Their main adverse effects are gastrointestinal bleeding, renal impairment and myocardial infarction with long-term use.^12–15 Postoperative pain can be effectively managed with NSAIDs, and NSAIDs have been shown to reduce opioid consumption in postoperative patients.¹⁶Given how commonly these medications are used, and the uncertainty in their comparative efficacy and safety, we sought to compare pain and safety outcomes for codeine-based medications and NSAIDs among adults who underwent outpatient surgery through a systematic review and meta-analysis of randomized controlled trials (RCTs).     

Phytalgic®, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial

Introduction

The medicinal treatment of osteoarthritis (OA) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), drugs with well-known risks. Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs. This study tested the effects of a food supplement, Phytalgic^®, on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs.

Methods

A randomized double-blind parallel-groups clinical trial compared Phytalgic^® (fish-oil, vitamin E, Urtica dioica) to a placebo for three months, in 81 patients with OA of the knee or hip using NSAIDs and/or analgesics regularly. The main outcome measures were use of NSAIDs (in Defined Daily Doses per day - DDD/day) or analgesics (in 500 mg paracetamol-equivalent tablets per week (PET/week) measured each month, and Western Ontario-McMaster University Osteo-Arthritis Index (WOMAC) function scales.

Results

After three months of treatment, the mean use of analgesics in the active arm (6.5 PET/week) vs. the placebo arm (16.5) was significantly different (P < 0.001) with a group mean difference of -10.0 (95% CI: -4.9 to -15.1). That of NSAIDs in the active arm (0.4 DDD/day) vs the placebo arm (1.0 DDD/day) was significantly different (P = 0.02) with a group mean difference of - 0.7 DDD/day (95% CI: -0.2 to -1.2). Mean WOMAC scores for pain, stiffness and function in the active arm (respectively 86.5, 41.4 and 301.6) vs the placebo arm (resp. 235.3, 96.3 and 746.5) were significantly different (P < 0.001) with group mean differences respectively of -148.8 (95% CI: -97.7 to -199.9), -54.9 (95% CI: -27.9 to -81.9) and -444.8 (95% CI: -269.1 to -620.4).

Conclusions

The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis.

Trial registration

Clinicaltrials.gov NCT00666523.     

Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials

Introduction

In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS).

Methods

A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD −0.42; 95% CI [−0.61, −0.24]; P < 0.00001; I² = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD −0.40; 95% CI [−0.62, −0.18]; P = 0.0004; I² = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC).BT in mineral/thermal water (5 studies, 177 participants; 3 high-risk and 2 unclear risk studies) showed moderate evidence for a medium-to-large size reduction in pain and TPC at the end of treatment: SMD −0.84; 95% CI [−1.36, −0.31]; P = 0.002; I² = 63% and SMD −0.83; 95% CI [−1.42, −0.24]; P = 0.006; I² = 71%. After sensitivity analysis, and excluding one study, the effect size for pain decreased: SMD −0.58; 95% CI [−0.91, −0.26], P = 0.0004; I² = 0. Moderate evidence is given for a medium improvement of HRQOL (SMD −0.78; 95% CI [−1.13, −0.43]; P < 0.0001; I² = 0%). A significant effect on depressive symptoms was not found. The improvements for pain could be maintained at follow-up with smaller effects.

Conclusions

High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long-term results and maintenance of the beneficial effects.     

Effectiveness of moxibustion treatment as adjunctive therapy in osteoarthritis of the knee: a randomized,double-blinded,placebo-controlled clinical trial

Introduction

Our objective was to compare the effectiveness and safety of traditional Chinese moxibustion to that of sham moxibustion in patients with chronic knee osteoarthritis (KOA) pain.

Methods

We conducted a randomized placebo-controlled trial involving 110 patients with KOA who met the inclusion criteria. These patients randomly received either active moxibustion (n = 55) or sham moxibustion control (n = 55) at acupoints Dubi (ST 35), extra-point Neixiyan (EX-LE 4), and an Ashi (tender) point three times a week for 6 weeks. Effects were evaluated with Western Ontario and McMaster Universities’ Osteoarthritis Index (WOMAC VA 3.1) criteria at the end of the course of treatment and 3, 12, and 24 weeks after the initial treatment.

Results

The WOMAC pain scores showed greater improvement in the active treatment group than in control at weeks 3 (P = 0.012), 6 (P <0.001), 12 (P = 0.002), and 24 (P = 0.002) as did WOMAC physical function scores of the active treatment group at week 3 (P = 0.002), 6 (P = 0.015), and 12 (P <0.001) but not 24 (P = 0.058). Patients and practitioners were blinded successfully, and no significant adverse effects were found during the trial.

Conclusions

A 6-week course of moxibustion seems to relieve pain effectively and improve function in patients with KOA for up to 18 weeks after the end of treatment. Moxibustion treatment appears to be safe, and the usefulness of the novel moxa device was validated.

Trial registration

Current controlled trial: ISRCTN68475405. Registered 4 April 2014.     

Importance of attributes and willingness to pay for oral anticoagulant therapy in patients with atrial fibrillation in China: A discrete choice experiment

BackgroundAdherence to oral anticoagulant therapy in patients with atrial fibrillation (AF) in China is low. Patient preference, one of the main reasons for discontinuation of oral anticoagulant therapy, is an unfamiliar concept in China.Methods and findingsA discrete choice experiment (DCE) was conducted to quantify patient preference on 7 attributes of oral anticoagulant therapy: antidote (yes/no), food–drug interaction (yes/no), frequency of blood monitoring (no need, every 6/3/1 month[s]), risk of nonfatal major bleeding (0.7/3.1/5.5/7.8[%]), risk of nonfatal stroke (ischemic/hemorrhagic) or systemic embolism (0.6/3.2/5.8/8.4[%]), risk of nonfatal acute myocardial infarction (AMI) (0.2/1.0/1.8/2.5[%]), and monthly out-of-pocket cost (0/120/240/360 RMB) (0 to 56 USD). A total of 16 scenarios were generated by using D-Efficient design and were randomly divided into 2 blocks. Eligible patients were recruited and interviewed from outpatient and inpatient settings of 2 public hospitals in Beijing and Shenzhen, respectively. Patients were presented with 8 scenarios and asked to select 1 of 3 options: 2 unlabeled hypothetical treatments and 1 opt-out option. Mixed logit regression model was used for estimating patients’ preferences of attributes of oral anticoagulants and willingness to pay (WTP) with adjustments for age, sex, education level, income level, city, self-evaluated health score, histories of cardiovascular disease/other vascular disease/any stroke/any bleeding, and use of anticoagulant/antiplatelet therapy. A total of 506 patients were recruited between May 2018 and December 2019 (mean age 70.3 years, 42.1% women). Patients were mainly concerned about the risks of AMI (β: −1.03; 95% CI: −1.31, −0.75; p < 0.001), stroke or systemic embolism (β: −0.81; 95% CI: −0.90, −0.73; p < 0.001), and major bleeding (β: −0.69; 95% CI: −0.78, −0.60; p < 0.001) and were willing to pay more, from up to 798 RMB to 536 RMB (124 to 83 USD) monthly. The least concerning attribute was frequency of blood monitoring (β: −0.31; 95% CI: −0.39, −0.24; p < 0.001). Patients had more concerns about food–drug interactions even exceeding preferences on the 3 risks, if they had a history of stroke or bleeding (β: −2.47; 95% CI: −3.92, −1.02; p < 0.001), recruited from Beijing (β: −1.82; 95% CI: −2.56, −1.07; p < 0.001), or men (β: −0.96; 95% CI: −1.36, −0.56; p < 0.001). Patients with lower educational attainment or lower income weighted all attributes lower, and their WTP for incremental efficacy and safety was minimal. Since the patients were recruited from 2 major hospitals from developed cities in China, further studies with better representative samples would be needed.ConclusionsPatients with AF in China were mainly concerned about the safety and effectiveness of oral anticoagulant therapy. The preference weighting on food–drug interaction varied widely. Patients with lower educational attainment or income levels and less experience of bleeding or stroke had more reservations about paying for oral anticoagulant therapies with superior efficacy, safety, and convenience of use.

In a discrete choice experiment, Jiaxi Zhao and colleagues investigate the importance of attributes of oral anticoagulant therapy and willingness-to-pay in patients with atrial fibrillation in China.     

Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study

Background

Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.

Methods

118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.

Results

By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.

Conclusions

Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.     

Intensive Lifestyle Intervention Improves Physical Function Among Obese Adults With Knee Pain: Findings From the Look AHEAD Trial

Lifestyle interventions have resulted in weight loss or improved physical fitness among individuals with obesity, which may lead to improved physical function. This prospective investigation involved participants in the Action for Health in Diabetes (Look AHEAD) trial who reported knee pain at baseline (n = 2,203). The purposes of this investigation were to determine whether an Intensive Lifestyle Intervention (ILI) condition resulted in improvement in self‐reported physical function from baseline to 12 months vs. a Diabetes Support and Education (DSE) condition, and whether changes in weight or fitness mediated the effect of the ILI. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function subscales, and WOMAC summary score. ILI participants exhibited greater adjusted mean weight loss (s.e.) vs. DSE participants (?9.02 kg (0.48) vs. ?0.78 kg (0.49); P < 0.001)). ILI participants also demonstrated more favorable change in WOMAC summary scores vs. DSE participants (β (s.e.) = ?1.81 (0.63); P = 0.004). Multiple regression mediation analyses revealed that weight loss was a mediator of the effect of the ILI intervention on change in WOMAC pain, function, and summary scores (P < 0.001). In separate analyses, increased fitness also mediated the effect of the ILI intervention upon WOMAC summary score (P < 0.001). The ILI condition resulted in significant improvement in physical function among overweight and obese adults with diabetes and knee pain. The ILI condition also resulted in significant weight loss and improved fitness, which are possible mechanisms through which the ILI condition improved physical function.     

Mindfulness-Based Interventions for People Diagnosed with a Current Episode of an Anxiety or Depressive Disorder: A Meta-Analysis of Randomised Controlled Trials

Objective

Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder.

Method

Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed.

Results

Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81).

Conclusions

This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population.     

Moxibustion Treatment for Knee Osteoarthritis: A Multi-Centre,Non-Blinded,Randomised Controlled Trial on the Effectiveness and Safety of the Moxibustion Treatment versus Usual Care in Knee Osteoarthritis Patients

Introduction

This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety.

Methods

A multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40–70 were recruited from 2011–12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome.

Results

102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/−SD 19.26, UC 33.60+/−17.91, p<0.01, effect size  = 0.0477), NRS (moxibustion 44.77+/−22.73, UC 56.23+/−17.71, p<0.01, effect size  = 0.0073) and timed-stand test (moxibustion 24.79+/−9.76, UC 25.24+/−8.84, p = 0.0486, effect size  = 0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025) and social functioning (p = 0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n = 6) and second degree (n = 113) burns, pruritus and fatigue (n = 2).

Conclusions

Moxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding.

Trial Registration

Clinical Research Information Service (CRIS) KCT0000130     

Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip.

Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patient's global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.     

Phytalgic?, a food supplement,vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial

Introduction

The medicinal treatment of osteoarthritis (OA) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), drugs with well-known risks. Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs. This study tested the effects of a food supplement, Phytalgic^®, on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs.

Methods

A randomized double-blind parallel-groups clinical trial compared Phytalgic^® (fish-oil, vitamin E, Urtica dioica) to a placebo for three months, in 81 patients with OA of the knee or hip using NSAIDs and/or analgesics regularly. The main outcome measures were use of NSAIDs (in Defined Daily Doses per day - DDD/day) or analgesics (in 500 mg paracetamol-equivalent tablets per week (PET/week) measured each month, and Western Ontario-McMaster University Osteo-Arthritis Index (WOMAC) function scales.

Results

After three months of treatment, the mean use of analgesics in the active arm (6.5 PET/week) vs. the placebo arm (16.5) was significantly different (P < 0.001) with a group mean difference of -10.0 (95% CI: -4.9 to -15.1). That of NSAIDs in the active arm (0.4 DDD/day) vs the placebo arm (1.0 DDD/day) was significantly different (P = 0.02) with a group mean difference of - 0.7 DDD/day (95% CI: -0.2 to -1.2). Mean WOMAC scores for pain, stiffness and function in the active arm (respectively 86.5, 41.4 and 301.6) vs the placebo arm (resp. 235.3, 96.3 and 746.5) were significantly different (P < 0.001) with group mean differences respectively of -148.8 (95% CI: -97.7 to -199.9), -54.9 (95% CI: -27.9 to -81.9) and -444.8 (95% CI: -269.1 to -620.4).

Conclusions

The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00666523","term_id":"NCT00666523"}}NCT00666523.     

Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.

OBJECTIVE: To review the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions. DESIGN: Quantitative systematic review of randomised controlled trials. DATA SOURCES: 86 trials involving 10,160 patients. MAIN OUTCOME MEASURES: Measures of treatment success approximating at least 50% reduction in pain, local and systemic adverse effects. Analysis at 1 week for acute and 2 weeks for chronic conditions with relative benefit and number needed to treat. RESULTS: In acute pain conditions (soft tissue trauma, strains, and sprains) placebo controlled trials had a relative benefit of 1.7 (1.5 to 1.9), the number needed to treat was 3.9 (3.4 to 4.4). With analysis by drug (at least three trials), ketoprofen (number needed to treat 2.6), felbinac (3.0), ibuprofen (3.5), and piroxicam (4.2) had significant efficacy. Benzydamine and indomethacin were no different from placebo. In chronic pain conditions (osteoarthritis, tendinitis) placebo controlled trials had a relative benefit of 2.0 (1.5 to 2.7); the number needed to treat was 3.1 (2.7 to 3.8). Small trials (< 40 treated patients) exaggerated effectiveness of topical non-steroidals by 33% in acute conditions but not in chronic conditions. There was no relation between trial quality and treatment effect. In both acute and chronic pain local and systemic adverse events and withdrawal from the study related to the drug had a low incidence and were no different from placebo. CONCLUSION: Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.     

Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care

Objectives To measure the effectiveness and cost effectiveness of providing care in a chest pain observation unit compared with routine care for patients with acute, undifferentiated chest pain.Design Cluster randomised controlled trial, with 442 days randomised to the chest pain observation unit or routine care, and cost effectiveness analysis from a health service costing perspective.Setting The emergency department at the Northern General Hospital, Sheffield, United Kingdom.Participants 972 patients with acute, undifferentiated chest pain (479 attending on days when care was delivered in the chest pain observation unit, 493 on days of routine care) followed up until six months after initial attendance.Main outcome measures The proportion of participants admitted to hospital, the proportion with acute coronary syndrome sent home inappropriately, major adverse cardiac events over six months, health utility, hospital reattendance and readmission, and costs per patient to the health service.Results Use of a chest pain observation unit reduced the proportion of patients admitted from 54% to 37% (difference 17%, odds ratio 0.50, 95% confidence interval 0.39 to 0.65, P < 0.001) and the proportion discharged with acute coronary syndrome from 14% to 6% (8%, -7% to 23%, P = 0.264). Rates of cardiac event were unchanged. Care in the chest pain observation unit was associated with improved health utility during follow up (0.0137 quality adjusted life years gained, 95% confidence interval 0.0030 to 0.0254, P = 0.022) and a saving of £78 per patient (-£56 to £210, P = 0.252).Conclusions Care in a chest pain observation unit can improve outcomes and may reduce costs to the health service. It seems to be more effective and more cost effective than routine care.     

Gabapentin for the Management of Chronic Pelvic Pain in Women (GaPP1): A Pilot Randomised Controlled Trial

Chronic pelvic pain (CPP) affects 2.1–24% of women. Frequently, no underlying pathology is identified, and the pain is difficult to manage. Gabapentin is prescribed for CPP despite no robust evidence of efficacy. We performed a pilot trial in two UK centres to inform the planning of a future multicentre RCT to evaluate gabapentin in CPP management. Our primary objective was to determine levels of participant recruitment and retention. Secondary objectives included estimating potential effectiveness, acceptability to participants of trial methodology, and cost-effectiveness of gabapentin. Women with CPP and no obvious pelvic pathology were assigned to an increasing regimen of gabapentin (300-2700mg daily) or placebo. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to six months. The analyses by treatment group were by intention-to-treat. Interviews were conducted to evaluate women’s experiences of the trial. A probabilistic decision analytical model was used to estimate cost-effectiveness. Between September 2012–2013, 47 women (34% of those eligible) were randomised (22 to gabapentin, 25 to placebo), and 25 (53%) completed six-month follow-up. Participants on gabapentin had less pain (BPI difference 1.72 points, 95% CI:0.07–3.36), and an improvement in mood (HADS difference 4.35 points, 95% CI:1.97–6.73) at six months than those allocated placebo. The majority of participants described their trial experience favorably. At the UK threshold for willingness-to-pay, the probabilities of gabapentin or no treatment being cost-effective are similar. A pilot trial assessing gabapentin for CPP was feasible, but uncertainty remains, highlighting the need for a large definitive trial.

Trial registration

Controlled-Trials.com ISRCTN45178534